Quimio em casa: application for family members of children and adolescents using oral antineoplastic agents / Quimio en casa: aplicación para familiares de niños y adolescentes que usan antineoplásicos orales / Quimio em casa: aplicativo para familiares de crianças e adolescentes em uso de antineoplásicos orais

ABSTRACT Objective: to develop and validate a mobile application for the guidance of family members of children and adolescents undergoing treatment with oral antineoplastic drugs. Method: this is methodological research developed in seven steps: search for themes through interviews with twenty-three family members of children and adolescents undergoing oral chemotherapy; theoretical study; mobile application development; validation with thirteen expert judges; adequacy; validation with twelve family members of children and adolescents undergoing oral chemotherapy and mobile application final adaptation. The interviews were analyzed using the Interface de R pour Analyses Multidimensionnelles de Textes et de Questionneires software and validated with a Likert-type scale, considering validated items with a Concordance Index equal to or greater than 70%. Results: the application "Quimio em Casa" was returned with two interfaces, a desktop version aimed at health professionals and the application for family members of children and adolescents undergoing treatment with oral chemotherapy. The contents that guided the application development were storage, handling, administration, specific care for each chemotherapy agent, adverse effects, when to go to the emergency room and daily checking of administrations. The application was designed and validated with an adequacy Concordance Index of 96.7% among judges, and 100% by family members. Conclusion: the application proved to be valid as an educational technology in practical application with family members of children and adolescents undergoing oral chemotherapy.

RESUMEN Objetivo: desarrollar y validar una aplicación móvil para la orientación de familiares de niños y adolescentes en tratamiento con antineoplásicos orales. Método: investigación metodológica desarrollada en siete etapas: búsqueda de temas a través de entrevistas con veintitrés familiares de niños y adolescentes en quimioterapia oral; estudio teórico; desarrollo de aplicaciones móviles; validación con trece jueces expertos; adecuación; validación con doce familiares de niños y adolescentes en quimioterapia oral y adaptación final de la aplicación móvil. Las entrevistas fueron analizadas mediante el software Interface de R pour Analyses Multidimensionnelles de Textes et de Questionneires y validadas con la escala de Likert, considerando ítems con Índice de Concordancia igual o superior al 70% validados. Resultados: se devolvió la aplicación "Quimio em Casa" con dos interfaces, una versión de escritorio dirigida a profesionales de la salud y la aplicación para familiares de niños y adolescentes en tratamiento con quimioterapia oral. Los contenidos que orientaron el desarrollo de la aplicación fueron: almacenamiento; manipulación; administración; el cuidado específico de cada agente de quimioterapia; efectos adversos; cuándo acudir a urgencias y controles diarios de administración. La aplicación fue diseñada y validada con un Índice de Concordancia de Adecuación del 96,7% entre los jueces y del 100% por parte de los familiares. Conclusión: la aplicación demostró ser válida como tecnología educativa en aplicación práctica con familiares de niños y adolescentes en quimioterapia oral.

RESUMO Objetivo: elaborar e validar um aplicativo móvel para a orientação de familiares de crianças e adolescentes em tratamento com antineoplásicos orais. Método: pesquisa metodológica desenvolvida em sete etapas: busca dos temas por meio de entrevistas com vinte e três familiares de crianças e adolescentes em quimioterapia oral; estudo teórico; desenvolvimento do aplicativo móvel; validação com treze juízes especialistas; adequação; validação com doze familiares de crianças e adolescentes em quimioterapia oral e adequação final do aplicativo móvel. As entrevistas foram analisadas pelo software Interface de R pour Analyses Multidimensionnelles de Textes et de Questionneires e validadas com a escala Likert, considerando-se validados itens com Índice de Concordância igual ou maior a 70%. Resultados: o aplicativo "Quimio em Casa" foi devolvido com duas interfaces, uma versão desktop voltada para os profissionais de saúde e o aplicativo para os familiares de crianças e adolescentes em tratamento com quimioterápicos orais. Os conteúdos que direcionaram a elaboração do aplicativo foram: armazenamento; manipulação; administração; os cuidados específicos de cada quimioterápico; efeitos adversos; quando ir à emergência e checagem diária das administrações. O aplicativo foi elaborado e validado com Índice de Concordância de adequação de 96,7% entre os juízes, e de 100% pelos familiares. Conclusão: o aplicativo mostrou-se válido como tecnologia educacional na aplicação prática junto aos familiares de crianças e adolescentes em quimioterapia oral.

Standardization of the infusion sequence of antineoplastic drugs used in the treatment of breast and colorectal cancers / Padronização da ordem de infusão de medicamentos antineoplásicos utilizados no tratamento dos cânceres de mama e colorretal

ABSTRACT The definition of antineoplastic administration sequences can help planning of therapeutic regimens in a more rational way, and thus optimize chemotherapy effects on patients, increasing efficacy and reducing toxic effects. In this way, this study aimed to evaluate the infusion order of antineoplastic agents of the main therapeutic protocols used in the treatment of colorectal and breast cancer which are used in a tertiary hospital, identifying possible interactions dependent on the infusion sequence. For the definition of protocols adopted in the hospital, medical prescriptions were used in the period of January to March 2016 and a literature review was conducted to search for studies assessing the sequence of administering the selected regimens. The databases used were SciELO, LILACS and MEDLINE, in addition to Micromedex Solutions® and UpToDate®. A total of 19 protocols were identified for antineoplastic therapy, 11 for colorectal cancer and 8 for breast cancer. The selected articles provided evidence for administration order of 19 protocols, and three protocols did no report relevance of infusion sequence. Sequence-dependent interactions were mainly related to toxicity, pharmacokinetics and efficacy of the drug combination. The definition of the infusion sequence has a great impact on the optimization of therapy, increasing efficacy and safety of the protocols containing combined antineoplastic therapies.

RESUMO A definição de sequências de administração de antineoplásicos pode proporcionar o planejamento dos esquemas terapêuticos de forma mais racional e, assim, otimizar o efeito da quimioterapia nos pacientes, aumentando a eficácia e reduzindo o aparecimento de efeitos tóxicos. Desta forma, o objetivo deste estudo foi avaliar a ordem de infusão dos antineoplásicos constituintes dos principais protocolos terapêuticos para o tratamento dos cânceres de mama e colorretal utilizados em um hospital terciário, identificando possíveis interações dependentes da sequência de infusão. Para definição dos protocolos adotados na Instituição, foram utilizadas as prescrições no período de janeiro a março de 2016, sendo então realizada uma revisão de literatura, para buscar estudos que avaliaram a sequência de administração dos esquemas selecionados. Para tanto, as seguintes bases de dados foram utilizadas: SciELO, LILACS e MEDLINE, além das plataformas Micromedex Solutions® e UpToDate®. Foram identificados 19 protocolos para terapia antineoplásica, sendo 11 para câncer colorretal e 8 para câncer de mama. Os artigos selecionados forneceram evidências para ordem de administração de 19 protocolos, e em 3 protocolos, não foi evidenciada a relevância da sequência infusional. As interações dependentes de sequência foram principalmente relacionadas à toxicidade, farmacocinética e eficácia da combinação de fármacos. A definição da sequência infusional possui grande impacto na otimização da terapia, aumentando a eficácia e a segurança dos protocolos, contendo terapias combinadas de antineoplásicos.

Determination of serum levels of imatinib mesylate in patients with chronic myeloid leukemia: validation and application of a new analytical method to monitor treatment compliance.

OBJECTIVE: The goal of this study was to monitor imatinib mesylate therapeutically in the Tumor Biology Laboratory, Department of Hematology and Hemotherapy, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP). A simple and sensitive method to quantify imatinib and its metabolite (CGP74588) in human serum was developed and fully validated in order to monitor treatment compliance. METHODS: The method used to quantify these compounds in serum included protein precipitation extraction followed by instrumental analysis using high performance liquid chromatography coupled with mass spectrometry. The method was validated for several parameters, including selectivity, precision, accuracy, recovery and linearity. RESULTS: The parameters evaluated during the validation stage exhibited satisfactory results based on the Food and Drug Administration and the Brazilian Health Surveillance Agency (ANVISA) guidelines for validating bioanalytical methods. These parameters also showed a linear correlation greater than 0.99 for the concentration range between 0.500 µg/mL and 10.0 µg/mL and a total analysis time of 13 minutes per sample. This study includes results (imatinib serum concentrations) for 308 samples from patients being treated with imatinib mesylate. CONCLUSION: The method developed in this study was successfully validated and is being efficiently used to measure imatinib concentrations in samples from chronic myeloid leukemia patients to check treatment compliance. The imatinib serum levels of patients achieving a major molecular response were significantly higher than those of patients who did not achieve this result. These results are thus consistent with published reports concerning other populations.

Importance of monitoring and early switch to second generation tyrosine kinase inhibitors for the prognosis of patients with chronic myeloid leukemia with imatinib resistance or intolerance.

Imatinib mesylate was the first BCR-ABL-target agent approved for the treatment of chronic myeloid leukemia. Although most patients respond well to imatinib therapy, the literature shows that one third develops resistance or intolerance. The timing of second-line treatment after failure of initial treatment may have a significant impact on long-term outcome. Thus, appropriate monitoring to identify resistance and/or intolerance is crucial to early intervention with second generation tyrosine kinase inhibitors and attainment of better results.